Population-based Prostate Cancer Screening Research Articles

Early detection of prostate cancer-individualized, risk-adapted and successful

Population-based screening for prostate cancer (PC) is still controversially discussed. Furthermore, an organized, risk-adapted screening program is already being called for across Europe. Although large randomized controlled trials have shown that prostate-specific antigen (PSA)-based screening can significantly reduce PC-specific mortality, all known screening strategies still frequently lead to overdiagnosis and consecutively to overtreatment of clinically insignificant PC. This review article presents the current evidence regarding PC screening. The current German early detection program, which is based on the annually recommended digital rectal examination (DRE), lacks specificity and sensitivity. In Germany, an opportunistic PSA screening is currently being carried out, which is no longer recommended due to an unfavorable benefit-risk ratio. Since 2022, the European Commission has been calling for the development of organized, risk-adapted screening strategies that combine the PSA test with magnetic resonance imaging (MRI). The integration of MRI improves the detection of clinically relevant PC and reduces the overdiagnosis of low-risk cancers. In the future, an algorithm for early detection of PC needs to be developed, which, in an organized and personalized screening, combines the PSA test with MRI and possibly genetic markers. The early detection of prostate cancer should be organized at the population level and integrated into personalized, evidence-based screening strategies.

Population-based Screening for Prostate Cancer: Is it Time?

Population-based Screening for Prostate Cancer: Is it Time?

RE: Prevalence of MRI Lesions in Men Responding to a GP-Led Invitation for a Prostate Health Check: A Prospective Cohort Study

Controversy surrounds population-based screening for prostate cancer, which has typically relied on PSA level for risk stratification. This commentary examines the recent prospective trial examining the use of biphasic prostate MRI scans as a screening tool for prostate cancer. Using a reliable test, such as MRI prostate, at an earlier point along the diagnostic pathway, the authors provide a novel solution to a difficult problem. Further research is warranted to assess how biphasic MRI might be feasible at a population level.

Using "Age and Total-PSA" as the Main Indicators: The Results of Taizhou Integrated Prostate Screening (No 2).

The aim of the study was to analyze population-based prostate cancer (PCa) screening and the incidence of PCa among males ≥50 years of age residing in the Luqiao district of Taizhou, China. From October to December 2020, male residents ≥50 years of age were screened for serum total prostate-specific antigen (total-PSA). If t-PSA re-test levels persisted above 4 μg/L, subjects underwent further noninvasive examinations, including digital rectal examination or multiparameter magnetic resonance imaging (mpMRI) of the prostate. Subjects underwent prostate biopsy of pathological tissue based on t-PSA and mpMRI results. A total of 3524 (49.1%) residents participated in this PCa screening study. In total, 285 (8.1%) subjects exhibited t-PSA levels ≥4.0 μg/L and 112 (3.2%) underwent noninvasive examinations. Forty-two (1.2%) residents underwent prostate biopsy, of which 16 (0.45%) were diagnosed with PCa. Of those diagnosed with PCa, three (19%) had localized PCa (cT1-cT2N0M0), six (37%) had locally advanced PCa (cT3a- cT4N0-1M0), and seven (44%) had advanced metastatic PCa (M1). Unfortunately, 3477 (48.5%) residents did not participate in the study, mainly due to lack of awareness of PCa based on feedback from local health centers. Age and t-PSA were used as primary screening indicators and, when further combined with mpMRI and prostate biopsy, confirmed the diagnosis of PCa among participating residents. Although this was a relatively economical and convenient screening method, education and knowledge should be further enhanced to increase the participation rate in PCa screening programs.

Willingness-to-pay for a population-based-prostate-specific antigen screening for prostate cancer in Anambra State, Southeast, Nigeria: a contingent valuation study.

Early diagnosis of cancer precursors improves treatment outcomes. Organized screening for prostate cancer is still uncommon in Nigeria, and if it is added to the national health budget, it may necessitate additional co-financing alternatives. The study aims to evaluate the maximum willingness- to- pay amount and acceptability of a Population-based screening for prostate cancer among a group of Nigerian men. The study was a cross-sectional survey-based study conducted among men drawn from different districts of the state. The payment card elicitation format was used to estimate the average maximum WTP amount. Multivariate Logistic regression was used to evaluate the correlates of WTP. A total of 439(81.9%) participants were willing to pay for the screening while only 97(18.1%) of the participants rejected the screening. The average WTP amount was US$6.01(mean ± median ± SD 6.01±4.12±5.75). Residence and knowledge of the disease were the major predictors. The findings showed that men in Anambra state Nigerian were willing to pay an average of US$6.01 for the Population-based screening. Even though the stated WTP amount seems low compared to the conventional cost of opportunistic screening (between USD 21), the majority of the participants 439(81.9%) willing to pay for the screening should be capitalized upon in finding alternative financing options for the program.

Young Age on Starting Prostate-specific Antigen Testing Is Associated with a Greater Reduction in Prostate Cancer Mortality: 24-Year Follow-up of the Göteborg Randomized Population-based Prostate Cancer Screening Trial

BackgroundThe risk of death from prostate cancer (PC) depends on age, but the age at which to start prostate-specific antigen (PSA) screening remains uncertain. ObjectiveTo study the relationship between risk reduction for PC mortality and age at first PSA screening. Design, setting, and participantsThe randomized Göteborg-1 trial invited men for biennial PSA screening between the ages of 50 and 70 yr (screening, n = 10 000) or no invitation but exposure to opportunistic PSA testing (control, n = 10 000). InterventionRegular versus opportunistic PSA screening or no PSA. Outcome measurements and statistical analysisWe modeled the nonlinear association between starting age and the absolute risk reduction in PC mortality in three settings: (1) intention-to-screen (randomized arms); (2) historical control (screening group and 1990–1994 registry data); and (3) attendees only (screening attendees and matched controls). We tested whether the effect of screening on PC mortality depends on the age at starting screening by comparing survival models with and without an interaction between trial arm and age (intention-to-screen and attendees only). Results and limitationsYounger age on starting PSA testing was associated with a greater reduction in PC mortality. Starting screening at age 55 yr approximately halved the risk of PC death compared to first PSA at age 60 yr. The test of association between starting age and the effect of screening on PC mortality was slightly greater than the conventional level of statistical significance (p = 0.052) for the entire cohort, and statistically significant among attendees (p = 0.002). This study is limited by the low number of disease-specific deaths for men starting screening before age 55 yr and the difficulty in discriminating between the effect of starting age and screening duration. ConclusionsGiven that prior screening trials included men aged up to 70 yr on starting screening, our results suggest that the effect size reported in prior trials underestimates that of currently recommended programs starting at age 50–55 yr. Patient summaryIn this study from the Göteborg-1 trial, we looked at the effect of prostate-specific antigen (PSA) screening in reducing men’s risk of dying from prostate cancer given the age at which they begin testing. Starting at a younger age reduced the risk of prostate cancer death by a greater amount. We recommend that PSA screening should start no later than at age 55 yr.

Assessment of the effectiveness of clinical PSA concentration measurements in early prostate cancer detection

Introduction. Prostate cancer is a malignant neoplasm originating primarily in the peripheral zone of the prostate gland. A patient’s survival depends largely on the stage of the disease and the treatment method used, which is why early detection of the tumour plays an important role. One of the methods used for screening for prostate cancer is the measurement of prostate specific antigen (PSA) concentration. Material and methods. The analysis was based on the results of the research found in the systematic review. The fol­lowing sources of medical information were searched for secondary research: Medline ( via PubMed), Embase ( via Ovid), The Cochrane Library. The time range has been set to articles published between July 2011 and July 2021. Results. The inclusion criteria for a systematic review of the clinical effectiveness of PSA measurements in the early detection of prostate cancer were met by 5 secondary scientific evidence articles. Most of the evidence found showed an increase in the detection of prostate cancer after PSA testing. In case of stage III or IV tumours and the metastatic prostate cancer (CaP) variant, a statistically significant reduction in tumour detection was demonstrated. Most of the scientific evidence indicates a statistically insignificant effect of PSA screening on the risk of death due to CaP (with a diagnostic threshold of ≥4 ng/ml). Conclusions. Screening in the opportunistic variant aimed at prostate cancer with the use of PSA concentration is justified in men between 50 and 69 years of age, and in men <50 years of age should they have additional risk factors. Conversely, it seems unjustified to conduct population-based screening for prostate cancer.

Results from 22 years of Followup in the Göteborg Randomized Population-Based Prostate Cancer Screening Trial.

Purpose:Our goal was to analyze results from 22 years of followup in the Göteborg randomized prostate cancer (PC) screening trial.Materials and Methods:In December 1994, 20,000 men born 1930–1944 were randomly extracted from the Swedish population register and were randomized (1:1) into either a screening group (SG) or to a control group (CG). Men in the SG were repeatedly invited for biennial prostate specific antigen testing up to an average age of 69 years. Main endpoints were PC incidence and mortality (intention-to-screen principle).Results:After 22 years, 1,528 men in the SG and 1,124 men in the CG had been diagnosed with PC. In total, 112 PC deaths occurred in the SG and 158 in the CG. Compared with the CG, the SG showed a PC incidence rate ratio (RR) of 1.42 (95% CI, 1.31–1.53) and a PC mortality RR of 0.71 (95% CI, 0.55–0.91). The 22-year cumulative PC mortality rate was 1.55% (95% CI, 1.29–1.86) in the SG and 2.13% (95% CI, 1.83–2.49) in the CG. Correction for nonattendance (Cuzick method) yielded a RR of PC mortality of 0.59 (95% CI, 0.43–0.80). Number needed to invite and number needed to diagnose was estimated to 221 and 9, respectively. PC death risk was increased in the following groups: nontesting men, men entering the program after age 60 and men with >10 years of followup after screening termination.Conclusions:Prostate specific antigen-based screening substantially decreases PC mortality. However, not attending, starting after age 60 and stopping at age 70 seem to be major pitfalls regarding PC death risk.

Reimagining prostate cancer screening: the IMPACT of germline mutations.

Structured prostate-specific antigen (PSA) screening allows for the early detection of prostate cancer in men aged 55–69 years with a reduction in the incidence of metastatic disease at presentation and cancer-specific mortality at 16 year's follow-up. 1 Hugosson J Roobol MJ Månsson M et al. A 16-yr follow-up of the European randomized study of screening for prostate cancer. Eur Urol. 2019; 76: 43-51 Summary Full Text Full Text PDF PubMed Scopus (182) Google Scholar Population-based screening has been associated with a non-negligible risk of overdiagnosis (ie, the detection of cancers that would not have caused symptoms), which can be as high as 40%, and has limited its adoption at a large scale 2 Martin RM Donovan JL Turner EL et al. Effect of a low-intensity PSA-based screening intervention on prostate cancer mortality: the CAP randomized clinical trial. JAMA. 2018; 319: 883-895 Crossref PubMed Scopus (210) Google Scholar such that no national prostate cancer screening programmes exist in the USA and Europe. 3 Van Poppel H Hogenhout R Albers P van den Bergh RCN Barentsz JO Roobol MJ A European model for an organised risk-stratified early detection programme for prostate cancer. Eur Urol Oncol. 2021; (published online Aug 4)https://doi.org/10.1016/j.euo.2021.06.006 Summary Full Text Full Text PDF Scopus (11) Google Scholar Restricting the use of repeated PSA testing to men at risk of early-onset disease because of a family history of prostate cancer or germline mutations has been proposed as a means of improving the effectiveness of screening. 2 Martin RM Donovan JL Turner EL et al. Effect of a low-intensity PSA-based screening intervention on prostate cancer mortality: the CAP randomized clinical trial. JAMA. 2018; 319: 883-895 Crossref PubMed Scopus (210) Google Scholar , 4 Gandaglia G Albers P Abrahamsson PA et al. Structured population-based prostate-specific antigen screening for prostate cancer: the European Association of Urology Position in 2019. Eur Urol. 2019; 76: 142-150 Summary Full Text Full Text PDF PubMed Scopus (49) Google Scholar , 5 Page EC Bancroft EK Brook MN et al. Interim results from the IMPACT study: evidence for prostate-specific antigen screening in BRCA2 mutation carriers. Eur Urol. 2019; 76: 831-842 Summary Full Text Full Text PDF PubMed Scopus (89) Google Scholar A prospective prostate cancer screening programme for men with pathogenic variants in mismatch repair genes (IMPACT): initial results from an international prospective studyAfter the first screening round, carriers of MSH2 and MSH6 pathogenic variants had a higher incidence of prostate cancer compared with age-matched non-carrier controls. These findings support the use of targeted PSA screening in these men to identify those with clinically significant prostate cancer. Further annual screening rounds will need to confirm these findings. Full-Text PDF Open Access

All-Cause Mortality Risk in National Prostate Cancer Cohort: An Impact of Population-Based Prostate Cancer Screening.

The aim of this study is to evaluate all-cause mortality risk differences before and during prostate cancer screening, with a profound focus on the differences between screened and not-screened patient groups. Prostate cancer cases diagnosed between 1998 and 2016 were identified from the population-based Lithuanian Cancer Registry and linked with screening status in the National Health Insurance Fund database. The analysis was stratified by a period of diagnosis and screening status. Standardized mortality ratios (SMRs) were used to assess all-cause and cause-specific mortality risk. The SMRs were calculated by dividing the observed number of deaths among prostate cancer patients by the expected number of deaths from the general population. All-cause SMR (1.45 (95% CI 1.42–1.48)) in the pre-screening period was higher compared to the screening period (SMR = 1.17 (95% CI 1.15–1.19)). An increased all-cause mortality risk among prostate cancer patients was observed in the not-screened patient population (SMR = 1.76 (95% CI 1.71–1.82)), while all-cause mortality risk in the screened patient population was similar to the general population (SMR = 1.00 (95% CI 0.97–1.02)). Screened patients with localized stage of disease had lower all-cause mortality risk than the general population (SMR = 0.72 (95% CI 0.70–0.75)). In conclusion, men with prostate cancer in Lithuania had excess all-cause mortality risk compared to the general population. The all-cause mortality risk among screened patients was not higher than expected.

Cost-effectiveness of multiparametric magnetic resonance imaging and MRI-guided biopsy in a population-based prostate cancer screening setting using a micro-simulation model.

BackgroundThe introduction of multiparametric magnetic resonance imaging (mpMRI) and MRI‐guided biopsy has improved the diagnosis of prostate cancer. However, it remains uncertain whether it is cost‐effective, especially in a population‐based screening strategy.MethodsWe used a micro‐simulation model to assess the cost‐effectiveness of an MRI‐based prostate cancer screening in comparison to the classical prostate‐specific antigen (PSA) screening, at a population level. The test sensitivity parameters for the mpMRI and MRI‐guided biopsy, grade misclassification rates, utility estimates, and the unit costs of different interventions were obtained from literature. We assumed the same screening attendance rate and biopsy compliance rate for both strategies. A probabilistic sensitivity analysis, consisting of 1000 model runs, was performed to estimate a mean incremental cost‐effectiveness ratio (ICER) and assess uncertainty. A €20,000 willingness‐to‐pay (WTP) threshold per quality‐adjusted life year (QALY) gained, and a discounting rate of 3.5% was considered in the analysis.ResultsThe MRI‐based screening improved the life‐years (LY) and QALYs gained by 3.5 and 3, respectively, in comparison to the classical screening pathway. Based on the probabilistic sensitivity analyses, the MRI screening pathway leads to total discounted mean incremental costs of €15,413 (95% confidence interval (CI) of €14,556–€16,272) compared to the classical screening pathway. The corresponding discounted mean incremental QALYs gained was 1.36 (95% CI of 1.31–1.40), resulting in a mean ICER of €11,355 per QALY gained. At a WTP threshold of €20,000, the MRI screening pathway has about 84% chance to be more cost‐effective than the classical screening pathway.ConclusionsFor triennial screening from age 55–64, incorporation of mpMRI as a reflex test after a positive PSA test result with a subsequent MRI‐guided biopsy has a high probability to be more cost‐effective as compared with the classical prostate cancer screening pathway.

Aspirin, ibuprofen, and reduced risk of advanced colorectal adenoma incidence and recurrence and colorectal cancer in the PLCO Cancer Screening Trial.

Studying the differential impact of aspirin and other nonsteroidal anti-inflammatory drugs across the stages of colorectal neoplasia from early adenoma to cancer is critical for understanding the benefits of these widely used drugs. With 13 years of follow-up, the authors prospectively evaluated the association between aspirin and ibuprofen use and incident distal adenoma (1221 cases), recurrent adenoma (862 cases), and incident colorectal cancer (CRC; 2826 cases) among men and women in the population-based Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. With multivariable-adjusted models, odds ratio (ORs) and 95% confidence intervals (CIs) for adenoma incidence and recurrence and hazard ratios (HRs) and 95% CIs for incident CRC were determined. The authors observed a significantly reduced risk of incident adenoma with ibuprofen use (≥30 vs <4 pills per month: OR, 0.76 [95% CI, 0.60-0.95]; Ptrend = .04), particularly advanced adenoma (OR, 0.48 [95% CI, 0.28-0.83]; Ptrend = .005). Among those with a previous adenoma detected through screening, aspirin use was associated with a decreased risk of advanced recurrent adenoma (≥30 vs <4 pills per month: OR, 0.56 [95% CI, 0.36-0.87]; Ptrend = 0.006). Both aspirin (HR, 0.88 [95% CI, 0.81-0.96]; Ptrend <.0001) and ibuprofen use (HR, 0.81 [95% CI, 0.70-0.93); Ptrend = 0.003) ≥30 versus <4 pills per month were significantly associated with reduced CRC risk. In this large prospective study with long-term follow-up, a beneficial role for not only aspirin, but also ibuprofen, in preventing advanced adenoma and curbing progression to recurrence and cancer among older adults was observed.

The GÖTEBORG prostate cancer screening 2 trial: a prospective, randomised, population-based prostate cancer screening trial with prostate-specific antigen testing followed by magnetic resonance imaging of the prostate

Objective To describe the study design of the GÖTEBORG prostate cancer screening (PC) 2 (Göteborg-2), a prospective, randomised, population-based trial of PC screening. This trial evaluates whether prostate-specific antigen (PSA) testing followed by 3 Tesla prostate magnetic resonance imaging (MRI) and targeted biopsy can reduce overdiagnosis, while maintaining the detection of clinically significant cancer, compared to PSA-screening and systematic biopsy. Materials and methods A random sample of men 50–60 years in the Göteborg area, Sweden, identified from the Total Population Register, were randomised to either a screening or control group (CG). Participants in the screening group (SG) were further randomised into one of three arms: (1) PSA-test; if PSA ≥ 3 ng/mL, then MRI and systematic biopsy, plus targeted biopsy to suspicious lesions as per Prostate Imaging – Reporting and Data System, version 2 (PI-RADSv2) 3–5; (2) PSA-test; if PSA ≥ 3 ng/mL, then MRI, and targeted biopsy only if PI-RADSv2 3–5; (3) identical to Arm 2, except lower PSA-cut-off ≥1.8 ng/mL. The primary outcome is the detection rate of clinically insignificant PC (defined as Gleason Score 3 + 3 [Grade Group 1]) comparing all men with PSA ≥ 3 ng/mL in Arm 1 vs. Arm 2 + 3. Results Randomisation and enrolment started in September 2015. Accrual has hitherto resulted in 38,770 men randomised to the SG. The participation rate is 50%. Invitation to the first screening round was completed in June 2020. Conclusions The Göteborg-2 trial will provide new knowledge about the performance of prostate MRI in a screening setting.

Population-Based Prostate Cancer Screening With Magnetic Resonance Imaging or Ultrasonography

Screening for prostate cancer using prostate-specific antigen (PSA) testing can lead to problems of underdiagnosis and overdiagnosis. Short, noncontrast magnetic resonance imaging (MRI) or transrectal ultrasonography might overcome these limitations. To compare the performance of PSA testing, MRI, and ultrasonography as screening tests for prostate cancer. This prospective, population-based, blinded cohort study was conducted at 7 primary care practices and 2 imaging centers in the United Kingdom. Men 50 to 69 years of age were invited for prostate cancer screening from October 10, 2018, to May 15, 2019. All participants underwent screening with a PSA test, MRI (T2 weighted and diffusion), and ultrasonography (B-mode and shear wave elastography). The tests were independently interpreted without knowledge of other results. Both imaging tests were reported on a validated 5-point scale of suspicion. If any test result was positive, a systematic 12-core biopsy was performed. Additional image fusion-targeted biopsies were performed if the MRI or ultrasonography results were positive. The main outcome was the proportion of men with positive MRI or ultrasonography (defined as a score of 3-5 or 4-5) or PSA test (defined as PSA ≥3 μg/L) results. Key secondary outcomes were the number of clinically significant and clinically insignificant cancers detected if each test was used exclusively. Clinically significant cancer was defined as any Gleason score of 3+4 or higher. A total of 2034 men were invited to participate; of 411 who attended screening, 408 consented to receive all screening tests. The proportion with positive MRI results (score, 3-5) was higher than the proportion with positive PSA test results (72 [17.7%; 95% CI, 14.3%-21.8%] vs 40 [9.9%; 95% CI, 7.3%-13.2%]; P < .001). The proportion with positive ultrasonography results (score, 3-5) was also higher than the proportion of those with positive PSA test results (96 [23.7%; 95% CI, 19.8%-28.1%]; P < .001). For an imaging threshold of score 4 to 5, the proportion with positive MRI results was similar to the proportion with positive PSA test results (43 [10.6%; 95% CI, 7.9%-14.0%]; P = .71), as was the proportion with positive ultrasonography results (52 [12.8%; 95% CI, 9.9%-16.5%]; P = .15). The PSA test (≥3 ng/mL) detected 7 clinically significant cancers, an MRI score of 3 to 5 detected 14 cancers, an MRI score of 4 to 5 detected 11 cancers, an ultrasonography score of 3 to 5 detected 9 cancer, and an ultrasonography score of 4 to 5 detected 4 cancers. Clinically insignificant cancers were diagnosed by PSA testing in 6 cases, by an MRI score of 3 to 5 in 7 cases, an MRI score of 4 to 5 in 5 cases, an ultrasonography score of 3 to 5 in 13 cases, and an ultrasonography score of 4 to 5 in 7 cases. In this cohort study, when screening the general population for prostate cancer, MRI using a score of 4 or 5 to define a positive test result compared with PSA alone at 3 ng/mL or higher was associated with more men diagnosed with clinically significant cancer, without an increase in the number of men advised to undergo biopsy or overdiagnosed with clinically insignificant cancer. There was no evidence that ultrasonography would have better performance compared with PSA testing alone.

The comparative effectiveness of mpMRI and MRI-guided biopsy vs regular biopsy in a population-based PSA testing: a modeling study

The benefit of prostate cancer screening is counterbalanced by the risk of overdiagnosis and overtreatment. The use of a multi-parametric magnetic resonance imaging (mpMRI) test after a positive prostate-specific antigen (PSA) test followed by magnetic resonance imaging-guided biopsy (MRIGB) may reduce these harms. The aim of this study was to determine the effects of mpMRI and MRIGB vs the regular screening pathway in a population-based prostate cancer screening setting. A micro-simulation model was used to predict the effects of regular PSA screening (men with elevated PSA followed by TRUSGB) and MRI based screening (men with elevated PSA followed by mpMRI and MRIGB). We predicted reduction of overdiagnosis, harm-benefit ratio (overdiagnosis per cancer death averted), reduction in number of biopsies, detection of clinically significant cancer, prostate cancer death averted, life-years gained (LYG), and quality adjusted life years (QALYs) gained for both strategies. A univariate sensitivity analysis and threshold analysis were performed to assess uncertainty around the test sensitivity parameters used in the MRI strategy.In the MRI pathway, we predicted a 43% reduction in the risk of overdiagnosis, compared to the regular pathway. Similarly a lower harm-benefit ratio (overdiagnosis per cancer death averted) was predicted for this strategy compared to the regular screening pathway (1.0 vs 1.8 respectively). Prostate cancer mortality reduction, LY and QALYs gained were also slightly increased in the MRI pathway than the regular screening pathway. Furthermore, 30% of men with a positive PSA test could avoid a biopsy as compared to the regular screening pathway. Compared to regular PSA screening, the use of mpMRI as a triage test followed by MRIGB can substantially reduce the risk of overdiagnosis and improve the harm-benefit balance, while maximizing prostate cancer mortality reduction and QALYs gained.

The STHLM3-model, Risk-based Prostate Cancer Testing Identifies Men at High Risk Without Inducing Negative Psychosocial Effects

BackgroundThe new STHLM3 test, combining protein markers, genetic markers, and clinical data to assess a man’s prostate cancer (PCa) risk, has been investigated in Sweden within the frame of the STHLM3 trial. ObjectiveTo assess whether the STHLM3 test influences men’s worry level, PCa knowledge, attitude, and health-related quality of life (HRQoL). Design, setting, and participantsInvitations with login to the web survey were mailed to 10 000 men, 50–69 yr of age, who were eligible for the STHLM3 trial. The survey was sent 3 mo before invitation to the STHLM3 trial (baseline) and 5 mo after STHLM3 (follow-up). At baseline, the men were unaware of the upcoming invitation to STHLM3. The survey covered the following: PCa-specific worry and perceived vulnerability, knowledge about PCa, attitude toward PCa testing and health behavior, and HRQoL Outcome measurements and statistical analysisSurvey scores were compared between baseline and follow-up by using the nonparametric Wilcoxon-signed rank tests for paired samples. Analysis of covariance was performed for PCa risk group comparisons. Results and limitationsA total of 994 men (10%) responded to our survey at baseline and follow-up, and were assessed as follows: low risk: 421 men; intermediate risk: 421 men; and high risk:152, of whom 59 were diagnosed with PCa after further investigation. In men assessed as having low and intermediate risk, level of worrying decreased at follow-up (p < 0.001), whereas no changes were observed in men at high risk. Moreover, no HRQoL changes were observed over time. The low response rate is the main limitation. ConclusionsWe found that the STHLM3 model, a risk-based PCa test, showed no negative impact on the well-being of men. Patient summarySince our results suggest that the risk-based screening as used in STHLM3 did not induce negative psychological effects on the participants, we can recommend this risk-based approach for population-based prostate cancer screening.

Sojourn-time-corrected receiver operating characteristic curve (ROC) for prostate specific antigen (PSA) test in population-based prostate cancer screening

Evaluating the performance of serum prostate-specific antigen (PSA) test in population-based screening with receiver operating characteristics (ROC) curve often neglects the time dimension. Asymptomatic cases with negative PSA test would have been missed if sojourn time is not taken into account to allow for cases surfacing into the clinical phase. Data included 20,796 men with PSA test at the first screening round was used from population-based Finnish prostate cancer screening trial during 1996–1999. Cancers detected at the first screen, together with interval cancers ascertained during 4-year follow-up were expediently used to estimate sensitivity and specificity. A sojourn-time-corrected model was applied to estimating the possible false negative cases for those with PSA < 4 ng/ml for correcting the ROC curve. The estimated sensitivity estimate was reduced from 94.4% without correction to 68.8% with correction but the estimated specificity was identical (89.4% vs. 89.2%) at cutoff of 3 ng/ml. The corrected area under curve (AUC) [77.0% (74.9–79.1%)] of the PSA test was significantly lower than the uncorrected AUC [95.9% (95.3–96.6%)]. The failure of considering the time since last negative screen due to incomplete ascertainment for asymptomatic cancer led to the overestimation of PSA test performance that further affects the cut-off value of PSA tests for population-based prostate cancer screening.

Prostate Cancer Screening with PSA: Ten Years' Experience of Population Based Early Prostate Cancer Detection Programme in Lithuania.

The aim of this study is to report key performance estimates from the ten years of a population-based prostate cancer screening programme in Lithuania. Retrospective analysis of screening activities recorded in 2006–2015 among men aged 50–74 years was performed. We estimated screening coverage, cancer detection rate, compliance to biopsy, and positive predictive values in each screening round inside and outside the target population. In the first 10 years of screening, 16,061 prostate cancer cases were registered within the screening programme, 10,202 were observed among screened men but reported outside the screening programme, and 1455 prostate cancers were observed in a screening-naïve population. Screening cover reached up to 45.5% of the target population in the recent rounds. The proportion of prostate specific antigen (PSA) test-positive men decreased from 16.9% in 2006 to 10.7% in 2014–2015. Up to 40.0% of PSA test-positive men received a biopsy, of whom 42.0% were positive for prostate cancer. The cancer detection rate was 10.4−15.0% among PSA test-positives and 1.4–1.9% among screened individuals. Screening participants were more likely to be diagnosed with organ-confined disease as compared to non-participants. Despite the unorganized screening practices being employed and low coverage per screening round, 70% of the target population were screened at least once in the first 10 years of screening.

Rethinking prostate cancer screening: could MRI be an alternative screening test?

In the past decade rigorous debate has taken place about population-based screening for prostate cancer. Although screening by serum PSA levels can reduce prostate cancer-specific mortality, it is unclear whether the benefits outweigh the risks of false-positive results and overdiagnosis of insignificant prostate cancer, and it is not recommended for population-based screening. MRI screening for prostate cancer has the potential to be analogous to mammography for breast cancer or low-dose CT for lung cancer. A number of potential barriers and technical challenges need to be overcome in order to implement such a programme. We discuss different approaches to MRI screening that could address these challenges, including abbreviated MRI protocols, targeted MRI screening, longer rescreening intervals and a multi-modal screening pathway. These approaches need further investigation, and we propose a phased stepwise research framework to ensure proper evaluation of the use of a fast MRI examination as a screening test for prostate cancer.

Population-based prostate cancer screening using a prospective, blinded, paired screen-positive comparison of PSA and fast MRI: The IP1-PROSTAGRAM study.

5513 Background: The prostate-specific antigen (PSA) test can lead to under- and over-diagnosis of prostate cancer and has not been recommended for population screening. A fast MRI scan might overcome the limitations of PSA. IP1-PROSTAGRAM is the first study to evaluate the performance of a 15-minute non-contrast MRI for prostate cancer screening in comparison to PSA. Methods: IP1-PROSTAGRAM was a prospective, population-based, screen-positive paired-cohort study. Men aged 50-69 years in the UK were invited for prostate cancer screening through seven primary care practices or community-based recruitment. Participants underwent a PSA and MRI scan (T2-weighted and diffusion). MRI was scored using PIRADS version 2.0 without knowledge of PSA; screen-positive MRI (defined as either PIRADS score 3-5 or 4-5) were compared against a screen-positive PSA defined as ≥3ng/ml. If any test was screen-positive, a systematic 12-core biopsy was performed with MRI-ultrasound image-fusion targeted biopsy to MRI suspicious areas, as appropriate. Clinically-significant cancer was defined as any Gleason score ≥3+4. The primary outcome was the proportion of screen-positive MRI at different scores; important secondary outcomes were the number of clinically-significant and insignificant cancers detected. Results: 2034 men were invited to participate of whom 408 consented and 406 were screened by both PSA and MRI (10/Oct/2018-15/May/2019). The proportion with a screen-positive MRI (score 3-5) was higher than the proportion with a screen-positive PSA (17.7% [95%CI 14.3-21.8] vs. 9.9% [95%CI 7.3-13.2]; p &lt; 0.001). A screen-positive MRI (score 4-5) was similar to a screen-positive PSA (10.6% [95%CI 7.9-14.0] vs. 9.9% [95%CI 7.3-13.2], p = 0.71). An MRI score 3-5 or 4-5 used to denote a screen-positive MRI, compared to PSA alone, detected 14, 11 and 7 clinically-significant cancers, respectively. There were 7, 5 and 6 clinically-insignificant cancers detected, respectively. No serious adverse events occurred. Conclusions: When screening the general population for prostate cancer, MRI using a score of 4-5 to define a screen-positive test, compared to PSA alone at ≥3ng/ml, could lead to more men diagnosed with clinically-significant cancer without increasing the number of men biopsied or diagnosed with clinically-insignificant cancer. Clinical trial information: NCT03702439 .